Effects of Localized Neurotrophin Gene Expression on Spiral Ganglion Neuron Resprouting in the Deafened Cochlea

A cochlear implant may be used to electrically stimulate spiral ganglion neurons (SGNs) in people with severe sensorineural hearing loss (SNHL). However, these neurons progressively degenerate after SNHL due to loss of neurotrophins normally supplied by sensory hair cells (HCs). Experimentally, exogenous neurotrophin administration prevents SGN degeneration but can also result in abnormal resprouting of their peripheral fibers. This study aimed to create a target-derived neurotrophin source to increase neuron survival and redirect fiber resprouting following SNHL. Adenoviral (Ad) vectors expressing green fluorescent protein (GFP) alone or in combination with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3) were injected into the cochlear scala tympani or scala media of guinea-pigs (GPs) deafened via aminoglycosides for 1 week. After 3 weeks, cochleae were examined for gene expression, neuron survival, and the projection of peripheral fibers in response to gene expression. Injection of vectors into the scala media resulted in more localized gene expression than scala tympani injection with gene expression consistently observed within the partially degenerated organ of Corti. There was also greater neuron survival and evidence of localized fiber responses to neurotrophin-expressing cells within the organ of Corti from scala media injections (P < 0.05), a first step in promoting organized resprouting of auditory peripheral fibers via gene therapy.     

Human Hendra Virus Encephalitis Associated with Equine Outbreak, Australia, 2008

A recent Hendra virus outbreak at a veterinary clinic in Brisbane, Queensland, Australia, involved 5 equine and 2 human infections. In contrast to previous outbreaks, infected horses had predominantly encephalitic, rather than respiratory, signs. After an incubation period of 9–16 days, influenza-like illnesses developed in the 2 persons before progressing to encephalitis; 1 died. Both patients were given ribavirin. Basal serum and cerebrospinal fluid levels were 10–13 mg/L after intravenous administration and 6 mg/L after oral administration (isolate 90% inhibitory concentration 64 mg/L). Both patients were exposed to infected horses, 1 during the late incubation period in a horse. The attack rate for veterinary clinic staff exposed to infected horses was 10%. An isolate from this outbreak showed genetic heterogeneity with isolates from a concurrent, but geographically remote, outbreak and from previous outbreaks. Emergence of Hendra virus is a serious medical, veterinary, and public health challenge.     

Clarithromycin for experimental Staphylococcus aureus keratitis.

PURPOSE: Clarithromycin, a macrolide antibiotic not previously tested against the common causes of bacterial keratitis, was analyzed for its effectiveness in reducing the number of viable bacteria in a Staphylococcus keratitis model. An in vivo comparison of the effectiveness of clarithromycin to erythromycin, minocycline, and tetracycline for three strains of Staphylococcus aureus was done. METHODS: Rabbit eyes were intrastromally injected with 100 colony forming units of one of three strains of S. aureus. Two strains were methicillin-sensitive (ATCC 25923 and MSSA 309) and one strain methicillin-resistant (COL). Eyes were treated every 30 minutes with 0.3% clarithromycin, erythromycin, tetracycline, or minocycline from 4 to 9 hours postinfection. The number of colony forming units (CFU) per cornea in all eyes was determined at 10 hours postinfection. RESULTS: Vehicle-treated and untreated eyes (controls) contained over 6 logs of CFU per cornea, a value significantly higher than any of the antibiotic-treated eyes (P < or = 0.0001). Clarithromycin or erythromycin therapy significantly decreased the number of CFU per cornea by approximately 5 logs in the eyes infected with the methicillin-sensitive strains and by approximately 4 logs in the eyes infected with the methicillin-resistant strain. Tetracycline and minocycline were also successful in treating these strains, but overall showed less effectiveness than clarithromycin and erythromycin. CONCLUSIONS: Clarithromycin proved to be an effective ocular medication for the therapy of experimental S. aureus keratitis. The effectiveness of clarithromycin in this model and its known effectiveness for a variety of bacterial pathogens suggests a role for this drug as a useful ocular antibiotic.     

四种缓解化学药物治疗后骨髓抑制中成药对环磷酰胺所致小鼠血虚模型外周血和骨髓象的影响

目的:观察补气养血、健脾益肾的参芪颗粒,补气养血的复方阿胶浆,补气养阴的贞芪扶正颗粒,温肾健髓、益气养阴、生血止血的复方皂矾丸4种中成药对环磷酰胺所致小鼠血虚模型外周血及骨髓象的影响。方法:实验于2005-06/09在河南中医学院药理实验室完成。①选用健康昆明种成年小鼠150只,雌雄不拘。按随机数字表法分为15组,每组10只:高、中、低剂量贞芪扶正颗粒组分别按15,10,5g/kg(20mL/kg)剂量灌胃贞芪扶正颗粒混悬液(主要成分:黄芪、女贞子;甘肃扶正药业科技股份有限公司生产,批号040803);高、中、低剂量复方阿胶浆组分别按10,20,30mL/kg剂量灌胃复方阿胶浆(主要成分:阿胶、熟地黄、党参等;山东东阿阿胶股份有限公司生产,批号050446);高、中、低剂量复方皂矾丸组分别按2.4,1.6,0.8g/kg(20mL/kg)剂量灌胃复方皂矾丸混悬液(主要成分:皂矾、西洋参、海马等;陕西郝其军制药有限责任公司生产,批号041014);高、中、低剂量参芪颗粒组按3,2,1g/kg(0.2mL/10g)剂量灌胃参芪颗粒混悬液(主要成分:人参、黄芪、当归等;江西山高制药有限公司生产,批号040702);鲨肝醇组按10g(20mL)/kg剂量灌胃鲨肝醇混悬液;空白组和模型组灌胃同体积的生理盐水(0.2mL/10g)。每天给药1次,连续给药10d。从实验的第6天开始除空白组外,各组小鼠腹腔注射环磷酰胺40mg/kg,连续给药5d。②各组小鼠分别于末次给药后24h,进行血常规检测。另取右侧股骨,镜下计数骨髓有核细胞数。③计量资料符合正态分布、方差齐者用t检验。结果:小鼠150只均进入结果分析。①对外周血的影响:模型组小鼠血白细胞、红细胞和血小板计数及血红蛋白水平、血细胞比容均明显低于空白组(t=2.49～8.19,P<0.05￣0.01)。鲨肝醇组、各剂量参芪颗粒组和复方阿胶浆组及贞芪扶正颗粒组、复方皂矾丸组小鼠血白细胞计数均明显高于模型组(t=3.67～9.12,P<0.01)。中剂量复方阿胶浆组、贞芪扶正颗粒组和复方皂矾丸组和高剂量贞芪扶正颗粒组小鼠血红细胞计数明显高于模型组(t=2.58～3.05,P<0.05￣0.01)。高、中剂量复方阿胶浆组和中、低剂量贞芪扶正颗粒组小鼠血血小板计数明显高于模型组(t=2.48～2.84,P<0.05￣0.01)。各剂量复方阿胶浆组和各剂量贞芪扶正颗粒组和中、低剂量复方皂矾丸组小鼠血血红蛋白水平明显高于模型组(t=2.21～3.28,P<0.05￣0.01)。中剂量参芪颗粒组、各剂量复方阿胶浆组、高剂量贞芪扶正颗粒组,以及高、中剂量复方皂矾丸组小鼠血细胞比容明显高于模型组(t=2.15～2.86,P<0.05)。②对骨髓象的影响:与空白组比较,模型组小鼠骨髓有核细胞数均明显低于空白组(t=8.08,P<0.01)。鲨肝醇组,各剂量参芪颗粒组、复方阿胶浆组、贞芪扶正颗粒组、复方皂矾丸组小鼠骨髓有核细胞数明显高于模型组(t=3.05～5.67,P<0.01)。结论:参芪颗粒、复方阿胶浆、贞芪扶正颗粒、复方皂矾丸对环磷酰胺所致小鼠血虚模型外周血血细胞状况和骨髓象均有改善作用;其中贞芪扶正颗粒和复方皂矾丸对白细胞计数、红细胞计数的升高作用为优;贞芪扶正颗粒和复方阿胶浆对血小板计数升高作用为优;贞芪扶正颗粒、复方阿胶浆和复方皂矾丸对血红蛋白升高作用为优;4种中成药对血虚模型血细胞比容的影响相近;贞芪扶正颗粒对血虚模型有核细胞的升高作用为优。     

Rib stress fractures among rowers: definition, epidemiology, mechanisms, risk factors and effectiveness of injury prevention strategies

Rib stress fractures (RSFs) can have serious effects on rowing training and performance and accordingly represent an important topic for sports medicine practitioners. Therefore, the aim of this review is to outline the definition, epidemiology, mechanisms, intrinsic and extrinsic risk factors, injury management and injury prevention strategies for RSF in rowers. To this end, nine relevant books, 140 journal articles, the proceedings of five conferences and two unpublished presentations were reviewed after searches of electronic databases using the keywords 'rowing', 'rib', 'stress fracture', 'injury', 'mechanics' and 'kinetics'. The review showed that RSF is an incomplete fracture occurring from an imbalance between the rate of bone resorption and the rate of bone formation. RSF occurs in 8.1-16.4% of elite rowers, 2% of university rowers and 1% of junior elite rowers. Approximately 86% of rowing RSF cases with known locations occur in ribs four to eight, mostly along the anterolateral/lateral rib cage. Elite rowers are more likely to experience RSF than nonelite rowers. Injury occurrence is equal among sweep rowers and scullers, but the regional location of the injury differs. The mechanism of injury is multifactorial with numerous intrinsic and extrinsic risk factors contributing. Posterior-directed resultant forces arising from the forward directed force vector through the arms to the oar handle in combination with the force vector induced by the scapula retractors during mid-drive, or repetitive stress from the external obliques and rectus abdominis in the 'finish' position, may be responsible for RSF. Joint hypomobility, vertebral malalignment or low bone mineral density may be associated with RSF. Case studies have shown increased risk associated with amenorrhoea, low bone density or poor technique, in combination with increases in training volume. Training volume alone may have less effect on injury than other factors. Large differences in seat and handle velocity, sequential movement patterns, higher elbow-flexion to knee-extension strength ratios, higher seat-to-handle velocity during the initial drive, or higher shoulder angle excursion may result in RSF. Gearing may indirectly affect rib loading. Increased risk may be due to low calcium, low vitamin D, eating disorders, low testosterone or use of depot medroxyprogesterone injections. Injury management involves 1-2 weeks cessation of rowing with analgesic modalities followed by a slow return to rowing with low-impact intensity and modified pain-free training. Some evidence shows injury prevention strategies should focus on strengthening the serratus anterior, strengthening leg extensors, stretching the lumbar spine, increasing hip joint flexibility, reducing excessive protraction, training with ergometers on slides or floating-head ergometers, and calcium and vitamin D supplementation. Future research should focus on the epidemiology of RSF over 4-year Olympic cycles in elite rowers, the aetiology of the condition, and the effectiveness of RSF prevention strategies for injury incidence and performance in rowing.     

Experimental infection of horses with Hendra virus/Australia/horse/2008/Redlands

Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus harbored by Australian flying foxes with sporadic spillovers directly to horses. Although the mode and critical control points of HeV spillover to horses from flying foxes, and the risk for transmission from infected horses to other horses and humans, are poorly understood, we successfully established systemic HeV disease in 3 horses exposed to Hendra virus/Australia/Horse/2008/Redlands by the oronasal route, a plausible route for natural infection. In 2 of the 3 animals, HeV RNA was detected continually in nasal swabs from as early as 2 days postexposure, indicating that systemic spread of the virus may be preceded by local viral replication in the nasal cavity or nasopharynx. Our data suggest that a critical factor for reducing HeV exposure risk to humans includes early consideration of HeV in the differential diagnosis and institution of appropriate infection control procedures.     

Assessing implementation of comprehensive treatment models for young children with ASD: Reliability and validity of two measures

Treatment implementation is an under-studied and under-reported aspect of intervention studies involving individuals with autism spectrum disorder (ASD). One primary area of concern is the lack of reliable and valid implementation measures, which allows a conclusive association to be drawn between the intervention and participant outcomes. This study examined the psychometric properties of two implementation measures developed for comprehensive treatment models serving preschoolers with ASD (i.e., LEAP and TEACCH). Both of the measures were completed in classrooms using LEAP or TEACCH instructional approaches as well as in classrooms in which a business-as-usual or non-model specific treatment approach was used. Across four months of one school year, a maximum of 4 observations were conducted in each of the 34 classrooms involved in the study. Results indicated that both implementation tools are reliable and valid, and that particular subscales of these measures allowed for discrimination of the three types of classrooms from each other. This step of psychometrically validating implementation measures as part of conducting efficacy studies may yield more robust associations between implementation and intervention effects.